Lung cancer is the leading cause of cancer death in both men and women in the United States. Survival rate of lung cancer patients treated by conventional modalities remains far from satisfactory. Recently, new approaches in the treatment of lung cancer with novel drugs that selectively inhibit tumor blood supply thus controlling cancer cell survival, proliferation and/or metastasis in combination with conventional anticancer or antiangiogenic drugs have generated clinical interest. Our preliminary studies demonstrated that DIM-C-pPhC6H5 (DIM-P), a c substituted diindolylmethanes exhibits antiangiogenic activity. The objective of this proposal is to formulate targeted pegylated CREKA peptide coated nanocarriers of DIM-P (PCNCs-D) and investigate its antitumor activity and antiangiogenic potential for treatment of lung cancer. Our preliminary tube formation assay, western blot and immunohistochemistry studies strongly suggest that DIM-P and PCNCs-D exhibits antiangiogenic activity. Our hypothesis is: targeted pegylated nanocarriers of DIM-P will target tumor blood vasculature and increase plasma half life thereby inhibiting tumor growth by exerting antiangiogenic activity against lung tumors. The novel aspects of this proposal are to study the antiangiogenic efficacy of a novel targeted nanocarrier drug delivery therapy approach using PCNCs-D and to understand the molecular pathways involved in the antiangiogenic effect in an in vivo tumor model. The hypotheses and objectives of the proposed research shall be pursued with the following specific aims: (1) To formulate targeted nanocarriers of DIM-P; (2) To evaluate antiangiogenic and in vivo efficacy of targeted nanocarriers of DIM-P; and (3) To elucidate mechanism pathways involved in PCNCs-D activity in regressed tumors. The results emanating from these studies will demonstrate the usefulness of novel PCNCs-D as an effective targeted delivery of antiangiogenic drug for lung cancer treatment. The proposed studies have strong potential to demonstrate an untested and highly innovative approach for lung cancer treatment.